Andersons pediatric cardiology 1390
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Kawasakidisease.21Thecasefatalityrateis0.015%inJapan.3IntheUnited
States,reportedin-hospitalmortalityforKawasakidiseasehasvariedfrom0%
to0.17%.22,23Althoughthehighestriskofmyocardialinfarctionanddeath
occursinthefirstmonthsafterillnessonset,24suddendeathfromischemicheart
diseasemayoccurmanyyearslaterinpatientswithcoronaryarteryaneurysms
andstenoses.24,25
EtiologyandPathogenesis
ThecauseofKawasakidiseaseremainsunknowndespitedecadesof
investigationandcontroversy.Aninfectiouscauseortriggeringenetically
susceptibleindividualsisthemostwidelyacceptedtheory.Theself-limitedand
usuallynonrecurringnatureofthediseasesupportstheinfectiousetiology.
Moreover,theclinicalsignsandsymptomsoverlapwiththoseinknowntoxinmediatedorviralinfections.Predilectionofthediseaseforyoungchildren—
withrareoccurrenceinneonatesandadults—suggeststhatimmunityisacquired.
Aninfectiousagentisfurthersuggestedbywinter-springseasonality,outbreaks
inthecommunity,andoccasionalepidemics.Person-to-persontransmissiondoes
notoccur,butinfectionwithacommonagentcouldproduceasymptomatic
diseaseinmostchildrenandrecognizablesignsandsymptomsofthediseaseina
subsetofsusceptibleindividuals.
Manycandidatepathogenshavebeentestedanddiscarded.Morerecent
studiessuggestpossibleinfectionwithanovelRNAvirusthatentersthroughthe
upperrespiratorytract.26,27Thisconceptissupportedbyintracytoplasmic
inclusionbodiesinbronchialepithelialcellsandcoronaryarteriesofthe
majorityofpostmortemspecimensfromchildrenwithKawasakidiseasebutnot
incontrolpatients.Thenatureoftheantigenisstillundetermined,andeffortsto
characterizethemoleculardetailshavebeenlimitedbythepaucityofautopsy
tissueavailable.
Otherstudiesproposeanidiosyncraticimmuneresponse,influencedbyhost
genetics,thatistriggeredbyanenvironmentalexposurecarriedbywinds.28,29
ThistheoryissuggestedbylinksbetweentheseasonalityofKawasakidiseaseto
troposphericwindpatterns.
Theimportanceofgeneticfactorsinsusceptibilityissupportedbythe
influenceofraceandfamilyhistoryonitsincidence(seeEpidemiologysection).
Inaddition,anincreasingliteraturehasexploredtheassociationofgenetic
polymorphismstodiseasesusceptibilityortothedevelopmentof
aneurysms.30–45
Pathology
Kawasakidiseaseischaracterizedbysystemicinflammationofallmediumsized,muscular,intraparenchymalarteries,withthemostseriouscomplications
relatedtoinflammationofthecoronaryarteries.Peripheralarterialaneurysms—
especiallyoftheceliac,mesenteric,femoral,iliac,renal,axillaryandbrachial
arteries—canoccur,buttheyhavebeendescribedonlyinpatientswithcoronary
arteryaneurysms.46Arecentpathologicstudydescribedthreedistinct
vasculopathicprocesses.47Thefirstprocessisnecrotizingarteritis,whichisan
acuteself-limitedneutrophilicprocessthatprogressivelydestroysthearterial
wall.Thisisfollowedbysubacute/chronicvasculitis,anasynchronous
nonneutrophilicinflammatoryprocessofsmalllymphocytes.Itstartsinthefirst
2weeksofthediseasebutpersistsformonthstoyearsafterdiagnosis.Luminal
myofibroblasticproliferationisaprogressiveasynchronousintraluminal
stenosingprocessofsmoothmusclecell–derivedmyofibroblastsandtheirmatrix
products.
Theoutcomeofcoronaryaneurysmsdependsontheirseverity.Mildlydilated
andinflamedarteriesmaybeabletoremodeltonormal.However,large
aneurysmslosetheirintima,media,andelasticity,whichcannotberegenerated.
Aneurysmsmaydevelopthromboses,whichmaybecompletelyocclusivebut
alsomayorganize,recanalizeandcalcify(Fig.53.1).Arterieswithpartially
preservedmediacandevelopthrombosisorprogressivestenosisfromluminal
myofibroblasticproliferation.
